This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Efforts under Core 3 include the development of capabilities that: (1) increase and better define the certainty (pedigree and quality) of peptide, protein, and modified protein identifications;(2) and (3) enable analyses of larger datasets, pose and test hypotheses, and much more effectively develop new biological understandings or insights. Task 1: Implement methods for improved identification of peptides and modified peptides, and which also provide statistical measures of uncertainty within the context of comprehensive proteomics. Task 2: Development of software tools to support quantitative proteome measurements, including uncertainty estimates from relative peptide peak intensity data (i.e., using stable-isotope labeling) and corrected absolute intensity data. Task 3: Development of supporting software tools and usage protocols that combine information from peptide and intact protein level measurements to determine the nature of modifications. Task 4: The adoption and/or development of supporting tools and usage protocols for analysis of large proteome datasets and to conduct comparisons with expression array data. Supplemental funding has been provided to allow for public release of the advanced informatics tools developed under Core 3.